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γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation

Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We eval...

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Autores principales: Pratesi, Chiara, Zanussi, Stefania, Tedeschi, Rosamaria, Bortolin, Maria Teresa, Talamini, Renato, Rupolo, Maurizio, Scaini, Chiara, Basaglia, Giancarlo, Di Maso, Matteo, Mazzucato, Mario, Zanet, Ernesto, Tirelli, Umberto, Michieli, Mariagrazia, Carbone, Antonino, De Paoli, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323102/
https://www.ncbi.nlm.nih.gov/pubmed/25668032
http://dx.doi.org/10.1371/journal.pone.0116887
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author Pratesi, Chiara
Zanussi, Stefania
Tedeschi, Rosamaria
Bortolin, Maria Teresa
Talamini, Renato
Rupolo, Maurizio
Scaini, Chiara
Basaglia, Giancarlo
Di Maso, Matteo
Mazzucato, Mario
Zanet, Ernesto
Tirelli, Umberto
Michieli, Mariagrazia
Carbone, Antonino
De Paoli, Paolo
author_facet Pratesi, Chiara
Zanussi, Stefania
Tedeschi, Rosamaria
Bortolin, Maria Teresa
Talamini, Renato
Rupolo, Maurizio
Scaini, Chiara
Basaglia, Giancarlo
Di Maso, Matteo
Mazzucato, Mario
Zanet, Ernesto
Tirelli, Umberto
Michieli, Mariagrazia
Carbone, Antonino
De Paoli, Paolo
author_sort Pratesi, Chiara
collection PubMed
description Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12135 copies/mL) and 18 patients (median 417 copies/10(6) PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11–98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient’s therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT.
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spelling pubmed-43231022015-02-18 γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation Pratesi, Chiara Zanussi, Stefania Tedeschi, Rosamaria Bortolin, Maria Teresa Talamini, Renato Rupolo, Maurizio Scaini, Chiara Basaglia, Giancarlo Di Maso, Matteo Mazzucato, Mario Zanet, Ernesto Tirelli, Umberto Michieli, Mariagrazia Carbone, Antonino De Paoli, Paolo PLoS One Research Article Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12135 copies/mL) and 18 patients (median 417 copies/10(6) PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11–98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient’s therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT. Public Library of Science 2015-02-10 /pmc/articles/PMC4323102/ /pubmed/25668032 http://dx.doi.org/10.1371/journal.pone.0116887 Text en © 2015 Pratesi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pratesi, Chiara
Zanussi, Stefania
Tedeschi, Rosamaria
Bortolin, Maria Teresa
Talamini, Renato
Rupolo, Maurizio
Scaini, Chiara
Basaglia, Giancarlo
Di Maso, Matteo
Mazzucato, Mario
Zanet, Ernesto
Tirelli, Umberto
Michieli, Mariagrazia
Carbone, Antonino
De Paoli, Paolo
γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation
title γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation
title_full γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation
title_fullStr γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation
title_full_unstemmed γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation
title_short γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation
title_sort γ-herpesvirus load as surrogate marker of early death in hiv-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323102/
https://www.ncbi.nlm.nih.gov/pubmed/25668032
http://dx.doi.org/10.1371/journal.pone.0116887
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